Predictors of hyperlactataemia among children presenting with malaria in a low transmission area in The Gambia.

BACKGROUND: Hyperlactataemia and metabolic acidosis are important risk factors for malaria death, but measuring lactate at the point of care is not financially viable in many resource-poor settings. This study aimed to identify combinations of routinely available parameters that could identify children at high risk of hyperlactataemia. METHODS: Using data from a study of Gambian children aged six months to 16 years with severe or uncomplicated malaria, logistic regression modelling with a forward stepwise model selection process was used to develop a predictive model for hyperlactataemia from routinely available demographic, clinical and laboratory parameters. Potential predictors of hyperlactataemia considered for the modelling process were patient characteristics (age, sex, prior use of anti-malarials, and weight percentile for age), respiratory symptoms (deep breathing, irregular respiration, use of accessory muscles of respiration, lung crepitations, grunting respiration, cough, and age-specific respiratory rate), other clinical parameters recorded at presentation (duration of symptoms, Blantyre coma score, number of convulsions prior to admission, axillary temperature, dehydration, severe prostration, splenomegaly) and laboratory measures from blood tests (percentage parasitaemia, white cell count, lymphocyte count, neutrophil count, monocyte count, platelet count, haemoglobin level, blood glucose level). RESULTS: 495 children were included, and 68 (14%) had laboratory-confirmed hyperlactataemia (lactate > 7 mmol/L). Four features were independently associated with increased hyperlactataemia risk in a multivariable age- and sex-adjusted model: lower Blantyre score (odds ratio (OR) compared to score 5 = 2.68 (95% CI, 1.03-6.96) for score 3-4 and 6.18 (95% CI, 2.24-17.07) for score 0-2, p = 0.001), higher percentage parasitaemia (OR = 1.07 (1.03-1.11) per 0031% increase, p < 0.001), high respiratory rate for age (OR = 3.09 (1.50-6.38) per unit increase, p = 0.002), and deep breathing (OR = 2.81 (1.20-6.60), p = 0.02). Cross-validated predictions from the final model achieved area under the receiver operating characteristic curve of 0.83. CONCLUSIONS: This study identified predictors of hyperlactataemia requiring only simple bedside clinical examination and blood film examination that can be carried out in resource-limited settings to quickly identify children at risk of dangerously raised lactate. A simple spreadsheet tool implementing the final model is supplied as supplementary material

Differences in osteocyte density and bone histomorphometry between men and women and between healthy and osteoporotic subjects

Bone defects related to osteoporosis develop with increasing age and differ between males and females. It is currently thought that the bone remodeling process is supervised by osteocytes in a strain-dependent manner. We have shown an altered response of osteocytes from osteoporotic patients to mechanical loading, and osteocyte density is reduced in osteoporotic patients, which might relate to imperfect bone remodeling, leading to lack of bone mass and strength. Hence, information on osteocyte density will contribute to a better understanding of bone biology in males and females and to the assessment of osteoporosis. Osteocyte density as well as conventional histomorphometric parameters of trabecular bone were determined in cancellous iliac crest bone of healthy postmenopausal women and men and of osteoporotic women and men. Osteocyte density was higher in healthy females than in healthy males and lower in osteoporotic females than in healthy females. Bone mass was reduced in osteoporotic patients, both male and female. In females, trabecular number was reduced, whereas in males, trabecular thickness was reduced and eroded surface was increased. There were no correlations between the parameter groups bone architecture, bone formation, bone resorption, and osteocyte density. These results are consistent with impaired osteoblast function in osteoporotic patients and with a different mechanism of bone loss between men and women, in which osteocyte density might play a role. The reduced osteocyte numbers in female osteoporotic patients might relate to imperfect bone remodeling leading to lack of bone mass and strength. © 2005 Springer Science+Business Media, Inc

Patient-Specific Biomechanical Modeling of Bone Strength Using Statistically-Derived Fabric Tensors.

Low trauma fractures are amongst the most frequently encountered problems in the clinical assessment and treatment of bones, with dramatic health consequences for individuals and high financial costs for health systems. Consequently, significant research efforts have been dedicated to the development of accurate computational models of bone biomechanics and strength. However, the estimation of the fabric tensors, which describe the microarchitecture of the bone, has proven to be challenging using in vivo imaging. On the other hand, existing research has shown that isotropic models do not produce accurate predictions of stress states within the bone, as the material properties of the trabecular bone are anisotropic. In this paper, we present the first biomechanical study that uses statistically-derived fabric tensors for the estimation of bone strength in order to obtain patient-specific results. We integrate a statistical predictive model of trabecular bone microarchitecture previously constructed from a sample of ex vivo micro-CT datasets within a biomechanical simulation workflow. We assess the accuracy and flexibility of the statistical approach by estimating fracture load for two different databases and bone sites, i.e., for the femur and the T12 vertebra. The results obtained demonstrate good agreement between the statistically-driven and micro-CT-based estimates, with concordance coefficients of 98.6 and 95.5% for the femur and vertebra datasets, respectively